How ribosomes make proteins in our cells

Venki Ramakrishnan was awarded the Nobel Prize for Chemistry in 2009 together with Ada Yonath and Tom Steitz. They used X-ray crystallography to determine the structure of ribosomes. Venki Ramakrishnan describes ribosomes as machines often made from a million atoms. They are found in all cells of the body and use the genetic information from our genes to produce proteins. Each cell contains thousands of proteins which form the basis of chemical reactions allowing our bodies to operate.

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Robyn Williams: Everyone in the following program has a genius-level IQ, except of course for me. I am a robot and I don't need an IQ.

[Music: Theme from The Lego Movie]

James Clerk Maxwell was a genius, he set the stage for Einstein. Adam Spencer is quite smart too. And my first guest in this Science Show which makes members of Mensa look like kids on training wheels has a Nobel Prize, and next week becomes president of the Royal Society of London. Venki Ramakrishnan won his prize for work on ribosomes. They are the basis of your existence. Think Lego, which is always awesome, and how the blocks, just like proteins, build your body part by part.

Venki Ramakrishnan: Well, you can think of our genes as storages of information. So each gene contains information on how to make a particular protein. And if you ask why is that important, we have thousands of proteins in each of our cells, and these proteins carry out much of the chemistry of the cell, as well as give it its structure. So your skin and connective tissue is made of a protein called collagen. Without that you wouldn't have any form, you'd be a blob.

And proteins are also antibodies, so they help fight off infection. If you sense heat or touch or if you see, it's because proteins are sensing these signals. There's a protein called rhodopsin in your eye which senses light and sends a signal to your brain. Haemoglobin is a protein that carries oxygen from your lungs to your tissues in the blood. So I've given you just a snippet of what proteins do. They carry out thousands of functions, and each of those proteins is made by carrying out the instructions encoded in our genes. And the way that's done is that these genes reside normally on DNA, except in the case of a few viruses.

RNA, like DNA, consists of four building blocks. One of them is slightly different, and of course a sugar is different in DNA and RNA, but otherwise they have a broadly similar chemical structure. So this process is called transcription, it's as if you are transcribing a message, copying it.

But then when you go to make proteins from RNA, you have to go to a completely different sort of polymer. Proteins are polymers that consist of building blocks of amino acids, and there are 20 what we call natural amino acids that most commonly occur, and there are a couple more that occur under very special circumstances. And then any other amino acids are obtained later by modifying these 22.

So how do you get to these 20 amino acids from a polymer that consists of only four types of building blocks? And so now you're going to a different sort of language, and so biologists call this process of protein synthesis 'translation' because you are going from the language of the genes to the language of the protein polymer.

And this is all done by a very large machine that consists of almost a million atoms, and that machine is called the ribosome. And you can think of it as threading the genetic message in the form of RNA through it, and it reads each unit on the messenger RNA which is called a codon which is a group of three bases. And corresponding to those three bases, the correct amino acid is brought into the ribosome by yet another RNA molecule called a transfer RNA or a tRNA molecule. So you can see that as it reads this message in one part of the ribosome it stitches together the amino acids to make up the protein polymer in a different part of the ribosome. So when it's all done it has read the genetic instructions and made the appropriate protein. And this is going on constantly in essentially all of the cells in our body.

Robyn Williams: All the time?

Venki Ramakrishnan: All the time, and has been since life as we know it today, all forms of life today, evolved.

Robyn Williams: Is the ribosome the centre for multiple creation of these macromolecules? In other words, is this large factory doing something with 10, 20 or even more processes like that?

Venki Ramakrishnan: Yes, not only are ribosomes translating lots of messenger RNA simultaneously, that is to say they are making completely different proteins at any given time in the cell, but even the same message has multiple ribosomes on it. So if you look at an electron micrograph of a translating cell, what you see is this long string of particular messenger RNA and lots of ribosomes spaced out along it. So it's as if the first ribosome attaches, starts making protein, and as it moves along the mRNA, long before it's even done, the next ribosome is attached to it. So not only are they translating many different messages and many different kinds of messages, but the same message is being worked on by many ribosomes at the same time.

Robyn Williams: And we're all doing it all the time in all of our cells and it's keeping us alive and isn't that extraordinary. But what was your particular role in elucidating this process?

Venki Ramakrishnan: Well, if you want to understand how a very large, complicated process works, you need to understand what the components look like. And the ribosome is an enormous molecule. In fact it consists of many different proteins, all assembled around a core of large RNA molecules. So it was very difficult to know how it would work precisely, how did it actually recognise messenger RNA, how are the amino acids linked in the catalytic site of the ribosome? How did it move once it had formed the link? It then had to bring in the next amino acid, and so it had to move along the mRNA, and how did the tRNAs come in and then go through the ribosome and get ejected? So you can see this is a complicated machine.

The analogy I like to say is if you were, say, a Martian and had first looked at Earth and you saw these things moving around along these lanes which we call roads, and at first sight all you would see is that the creatures got in these little bug-like things, and then it would start moving, and then it would stop and creatures would get out. And in the process it would consume petrol and emit carbon dioxide and water and generate some heat, as well as movement.

You would understand a car at some level, but if you wanted to understand how that car actually worked then you would have to open up the hood and you would have to look and see how it was constructed and how firing a spark would result in combustion of the petrol and how that would generate a force on the cylinder which would then be connected through a crankshaft to the wheels and then there would be a steering wheel that would tell it what direction to go and there'd be brakes to stop it and so on.

So you need to understand what things look like, and not just look like in one stage but look like at many different steps of the process. And so what my laboratory, as well as a number of other groups did, was to determine the atomic structure of the ribosome, so we could understand precisely how all these hundreds of thousands of atoms in the ribosome where arranged in three dimensions. And we used a technique called x-ray crystallography, which was invented in Cambridge, to do that. That was just the beginning of trying to understand it, that allowed biochemists to do lots of sophisticated experiments and geneticists to modify things and see how it affected function.

But also we as a people who determine structures tried to trap the ribosome at different stages along this process, and so that's getting at snapshots of a movie and constructing a movie of how the machine works. And that has been quite instructive. But of course, lots of people have contributed to it and lots of different techniques have contributed to it.

Robyn Williams: But you got the Nobel Prize.

Venki Ramakrishnan: Yes. Well, I think probably the Nobel committee felt that determining that atomic structure transformed the field to a completely different level. You could ask much more sophisticated questions and have a much better understanding of how it worked, whereas if it were a black box, you were greatly limited by…for example, with the car analogy, if you simply didn't know what it looked like, you'd be very limited in your understanding of how a car worked.

Robyn Williams: Professor Venki Ramakrishnan, at Trinity College in Cambridge. He is the next president of the Royal Society of London, successor to Newton and Florey, and the first Indian to be in that position. He mentioned x-ray crystallography just now, yes, invented in Cambridge by a young man from Adelaide and his dad. And a bust of William Bragg will be unveiled by the Governor of South Australia next Wednesday at Government House in Adelaide. More from Venki Ramakrishnan next week.